Anthelmintic chemical compounds are widely known agents that are destructive to worms and used for treating internal and external parasitic infestations in animals including humans.
There are many different types of anthelmintic compound, each with varying degrees of parasitic activity and chemical properties.
A difficulty in formulating such compounds is that many are extremely insoluble in aqueous environments such as extracellular fluids thus they need to be formulated to ensure they are bioavailable. In addition, in order to make these compounds soluble, different conditions may be required resulting in situations where one compound may be solubilized by for example, by reducing pH. This change can cause other compounds in the formulation to become insoluble, or the change may cause physical or chemical degradation of another compound in the formulation. In addition, the change may cause adverse side effects in the animal.
Stabilising and providing combinations of anthelmintic agents for oral administration have been considered in the prior art. A wide variety of advantages may be obtained by such combinations and these are discussed in prior art patent specifications including WO 00/74489 and WO 02/09764, incorporated herein by reference.
In the present invention, an aim is to provide a tablet formulation containing at least one lipophilic compound that has anthelmintic activity that presents the active in a bioavailable form.
The macrocyclic lactone family of anthelmintic compounds, which family includes abamectin and ivermectin, present a difficult challenge in formulation as such compounds are largely insoluble in aqueous environments such as in an animal's body. An important factor is to ensure that the tablet dissolves on administration and releases the active agent or agents in a form that is bioavailable and does not simply pass through the animal without achieving the desired therapeutic effect.
One attempt to address the above problem is an ivermectin capsule for the treatment of internal and external parasites in adult sheep and lambs (marketed in New Zealand as IVOMEC® MAXIMIZER™ CR). This product is formulated to provide a slow release of ivermectin to ‘control’ parasites over a time period of 100 days. A disadvantage of this product is the continuous release of ivermectin at levels below that required to kill adult parasites. The drug levels are designed to the kill incoming larvae, which require a lower dose rate for control than adult parasites. Besides not addressing adult parasites, use of the product may lead to drug resistance where the low dose allows adult parasites to become resistant to the ivermectin. Further reinforcing the resistance problem is that, when this product is given to adult ewes, drug resistant parasites may also be transferred to progeny from the ewes prolonging resistance across different generations. A further problem with the above slow release capsule is that the time period between delivery and slaughter must be sufficiently long to ensure all agent has been released. By contrast, fast release products are more flexible as the time period between delivery and slaughter may be significantly shorter.
It should be appreciated that it is desirable to have a formulation:                for delivery of parasiticidal compounds including lipophilic agents,        which stabilises these agents so that they may be stored over time with minimal physical or chemical degradation, and,        delivers a consistent dose of the agents on administration to an animal.        
It is an object of the present invention to address the foregoing problems or at least to provide the public with a useful choice.
All references, including any patents or patent applications cited in this specification are hereby incorporated by reference. No admission is made that any reference constitutes prior art. The discussion of the references states what their authors assert, and the applicants reserve the right to challenge the accuracy and pertinency of the cited documents. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents form part of the common general knowledge in the art, in New Zealand or in any other country.
It is acknowledged that the term ‘comprise’ may, under varying jurisdictions, be attributed with either an exclusive or an inclusive meaning. For the purpose of this specification, and unless otherwise noted, the term ‘comprise’ shall have an inclusive meaning—i.e. that it will be taken to mean an inclusion of not only the listed components it directly references, but also other non-specified components or elements. This rationale will also be used when the term ‘comprised’ or ‘comprising’ is used in relation to one or more steps in a method or process. Further aspects and advantages of the present invention will become apparent from the ensuing description which is given by way of example only.